Mechanisms of bone cancer pain

骨癌疼痛的机制

基本信息

批准号：
16390455
负责人：
NAMIKI Akiyoshi
金额：
$ 8.9万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Although mu opioid receptor (MOR) agonists are used in treating most type of pain, a recent study suggested that the sensitivity of bone cancer pain to morphine was lower than that of inflammatory pain. However, the reasons for this have remained unclear. In this study, MOR expression and the analgesic effects of morphine in a bone cancer model were compared with those in an inflammatory pain model. A bone cancer pain model and an inflammatory pain model were made by injection of sarcoma cells into the intramedullary space of the femur and hindpaw injection of complete Freund's adjuvant (CFA), respectively. In behavioral study, mice with sarcoma injection showed flinching behavior of comparable magnitude induced by CFA-induced inflammation. Both intraperitoneal and intrathecal morphine was less effective on flinching behavior of mice with bone cancer than that of mice with CFA injection. Western blot analysis showed that MOR expression in dorsal root ganglion (DRG) ipsilateral to sarcoma injection was significantly reduced, while that ipsilateral to CFA injection was increased. In mice with sarcoma injection, the percentage of MOR-positive DRG neurons was lower than that in control mice (30.3% vs. 45.2%, respectively). In particular, MOR expression was reduced among CGRP- and TRPV1-positive DRG neurons, which are believed to be nociceptive (from 61.5% to 41.5% and from 72.1% to 48.4%, respectively). These results suggest that down-regulation of MOR in a distinct population of DRG neurons contribute to the relative inefficacy of morphine in treating bone cancer pain.

尽管使用MU阿片受体（MOR）激动剂用于治疗大多数类型的疼痛，但最近的一项研究表明，骨癌疼痛对吗啡的敏感性低于炎症性疼痛。但是，造成这种情况的原因尚不清楚。在这项研究中，将MOR的表达和吗啡在骨癌模型中的镇痛作用与炎症模型中的MOR表达和镇痛作用进行了比较。骨癌疼痛模型和炎症性疼痛模型分别通过将肉瘤细胞注射到股骨的髓内空间和后爪注射完整的Freund佐剂（CFA）。在行为研究中，注射肉瘤的小鼠表现出CFA诱导的炎症引起的可比幅度的畏缩行为。腹膜内和鞘内吗啡对骨癌小鼠的畏缩行为的有效性低，而不是注射CFA的小鼠。蛋白质印迹分析表明，在背侧神经节（DRG）对肉瘤注射的同侧的MOR表达显着降低，而同侧至CFA注射的注射量增加。在肉瘤注射的小鼠中，MOR阳性DRG神经元的百分比低于对照小鼠的百分比（分别为30.3％和45.2％）。特别是，在CGRP和TRPV1阳性DRG神经元之间降低了MOR的表达，据信它们具有伤害性（分别从61.5％到41.5％，从72.1％到48.4％）。这些结果表明，不同DRG神经元中MOR的下调有助于吗啡在治疗骨癌疼痛中的相对效率低下。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of Prostaglandin Receptor Subtype EP_1 in Prostaglandin E_2-induced nociceptive transmission in the rat spinal dorsal horn.

前列腺素受体亚型 EP_1 在前列腺素 E_2 诱导的大鼠脊髓背角伤害性传递中的作用。

DOI：
发表时间：
2004
期刊：
Brain Research 1010
影响因子：
0
作者：
Nakayama Y;Omote K
通讯作者：
Omote K

Use of percutaneous cardiopulmonary support in catastrophic massive pulmonary fat embolism.

经皮心肺支持在灾难性的大量肺脂肪栓塞中的应用。

DOI：
发表时间：
2006
期刊：
Br J Anaesth 96
影响因子：
0
作者：
Hirasawa H;Sakai A;Nakamura T;et. al.;Kawamata T;Kawamata M;Iwasaki S;Kawamata M.;Igarashi M.
通讯作者：
Igarashi M.

Effects of halothane and isoflurane on hyperexcitability of spinal dorsal horn neurons after incision in the rat.

氟烷和异氟烷对大鼠切口后脊髓背角神经元过度兴奋的影响。

DOI：
发表时间：
2005
期刊：
Anesthesiology 102
影响因子：
0
作者：
Kawamata M;Narimatsu E;Kozuka Y;Takahashi T;Sugino S;Niiya T;Namiki A.
通讯作者：
Namiki A.

The addition of epidural morphine to ropivacaine improves epidural analgesia after lower abdominal surgery

罗哌卡因中加入硬膜外吗啡改善下腹部手术后硬膜外镇痛

DOI：
发表时间：
2005
期刊：
Canadian Journal of Anaesthesia 52
影响因子：
0
作者：
Omae T;Kakihana Y;Matsunaga A;Tsuneyoshi I;Kawasaki K;Kanmura Y;Sakata R;垣花泰之;Yamamoto H;Niiyama Y
通讯作者：
Niiyama Y

Contribution of Interaction between Nitric Oxide and Cyclooxygenases to the Production of Prostaglandins in Carrageenan-induced Inflammation